The present invention relates to the use of chitosan and glycomacropeptide for the preparation of food, beverage, and dietary supplement products intended for promoting weight loss through appetite control, e.g., inducing satiety and reducing appetite, as well as lowering of serum cholesterol and lipids.
Appetite control in animals is physiologically complex. Some important factors include emotional state, the physical state of the stomach and intestine, and the levels of multiple hormones. Cholecystokinin (CCK) is a hormone produced by cells of the intestinal epithelium in response to signals triggered by intake of nutrients. It is believed to be an important hormone for appetite regulation. CCK acts at multiple sites in the body, including the brain.
It is known that increased CCK levels decreases appetite and slows the rate of gastric emptying. Therefore, enhancing the onset of CCK production increases the total levels of CCK secreted, which results in a reduction of appetite, thereby decreasing the total amount of food consumed. Additionally, increased levels of CCK also result in inducing satiety, which is a state characterized by a reduced interest and perceived need for food. Long term increases in CCK result in a benefit of weight loss or reduced weight gain. Additionally, decreasing food consumption generally provides an improvement in the levels of serum cholesterol and total lipids.
CCK production is controlled by, among other things, a feedback control based upon the presence of bile acids, which are surfactant-like molecules and improve fat digestion by aiding in the dispersion and emulsification of fat or lipids.
After production in the liver, bile acids are stored in the gall bladder, which contracts and releases bile acids into the intestine in response to CCK. One group concluded that the presence of physiologic concentrations free of bile acids suppress CCK production. I. Koop et al., Physiological Control of Cholecystokinin Release and Pancreatic Enzyme Secretion by Intraduodenal Bile Acids, Gut 39:661-667(1996).
Chitosan is an anionic polymer that is sometimes produced by the hydrolysis of crustacean shells. U.S. Pat. Nos. 4,223,023 and 5,932,561 disclose that chitosan binds to lipids. The resulting bound complex is resistant to digestion and absorption and is excreted in relatively unaltered form in the feces. As a result, the body is deprived of the large number of calories. Consequently, chitosan is widely used in food and dietary supplement products to promote weight loss.
U.S. Pat. No. 5,932,561 also discloses that chitosan reduces the amount of cholesterol available for absorption and assimilation by the body. Additionally, it has been found to reduce serum cholesterol levels. Cholesterol lowering by chitosan was extensively reviewed by J. W. Anderson et al. Soluble Fiber, pp. 339-363, in Dietary Fiber, Chemistry, Physiology, and Health Effects, eds. D. Kritchevsky, C. Bonfield, J. W. Anderson, Plenum Press, New York(1990). It was found that dietary chitosan, on a per gram basis, was more effective than pectin, guar gum, psyllium, or oat bran in lowering serum cholesterol in rats.
U.S. Pat. No. 5, 932,561 further discloses that chitosan also binds bile acids. Bile acids, such as deoxycholic acid, bear some structural similarities to cholesterol. One group found that when rats were fed a diet supplemented with chitosan, the level of fecal excretion of bile acids was greater than that observed in animals consuming a control diet, or in animals that had been fed a diet supplemented with similar levels of glucomannan. C. M. Gallaher, et al., Cholesterol Reduction by Glucomannan and Chitosan Is Mediated by Changes in Cholesterol Absorption and Bile Acid and Fat Excretion in Rats, J. Nutrition 130:2753-2759(2000). Thus, it was concluded that chitosan bound bile acids so avidly that the normal process of resorption of bile acids in the lower intestine was disrupted, and the bile acids were excreted in the feces.
Glycomacropeptide (GMP) is a glycopeptide that is produced from the proteolytic cleavage of xcexa-casein, a major dairy milk protein. GMP is present in the whey stream of cheese making, and commercial materials include whey isolates of varying purity. For example, Armor Proteines (Saint Brice en Cogles, France) supplies a material that is about 14% GMP. Glanbia Ingredients (Madison, Wis.) also supplies a whey protein isolate that contains about 16% GMP.
GMP has been found to increase CCK levels. The original research on GMP was performed in the early 1990""s by M. Yvon, T. Corring, and colleagues at the Laboratoire de Recherches Laitieres, Rennes, France. Yvon et al., Effects of Caseinmacropeptide (CMP) on Digestion Regulation, Reprod. Nutr. Dev. 34:527-537 (1994). Yvon et al. described a material that they named casein macropeptide, or CMP, which was produced by the protease cleavage of xcexa-casein (xcexa-casein is one of four forms of casein found in diary milk, and represents 13% of casein). CMP was heterogeneous because of heterozygosity in the gene encoding the protein, as well as variation in the pattern of post-translational phosphorylation and glycosylation. Yvon et al. described four major fractions of CMP. Effects of Gastric Digestive Products from Casein on CCK Release by Intestinal Cells in Rats, J. Nutr. Biochem. 5:578-584(1994). The investigators infused each of four fractions into isolated rat ileal segments, and measured CCK release. Only one of the four fractions stimulated CCK production. A subsequent paper by these authors indicated that glycosylation of the peptide was necessary for increasing CCK levels, and CMP obtained from only one of the two genetic variants of bovine xcexa-casein (alpha variant) was effective. Effect of Caseinmacropeptide (CMP) on Cholecystokinin (CCK) Release in Rat, Reprod. Nutr. Dev. 34:613-614 (1994).
One study looked at the effects of ingested GMP on human CCK levels. Corring, T. et al., 1997 International Whey Conference, Abstracts of Paper Presentations, Chicago. This study involved six volunteers; two received 50 g of casein, two received 50 g of whey protein, and two received 25 mg of GMP (purified material that was a slightly glycosylated form of variant A). Serum CCK and gastrin levels were measured over four hours after ingestion of the test substances. All treatments increased CCK over baseline; casein produced a 350% increase, whey protein, a 415% increase, and GMP, a 268% increase. The results are especially surprising in light of the small amount of GMP consumed (casein and whey protein were consumed in levels 2000 times that of GMP). Interestingly, serum gastrin levels were increased by casein and whey protein, but not by GMP.
Numerous processes have been described for the enzymatic digestion of casein and the isolation of GMP. For example, see U.S. Pat. Nos. 4,427,658, 5,061,622, 5,075,424, 5,216,129, 5,278,288, 5,280,107, 5,780,439, and 5,968,586, which are incorporated herein by reference. Also, see T. Nakano and L. Ozimek, Purification of Glycomacropeptide from Caseinate Hydrolysate by Gel Chromatography and Treatment with Acidic Solution, J. of Food Science, 65:588-590 (2000), and M. Tanimoto, et al., Large Scale Preparation of xcexa-Casein Glycomacropeptide from Rennet Casein Whey, Biosci. Biotech. Biochem., 56:40-141 (1992), which are incorporated herein by reference.
From a pure lexicographical view, GMP and CMP are different terms. However, they have been used by those skilled in the art to describe essentially the same material. Therefore, these two terms are functionally equivalent. Additionally, this material has also been described in the literature as xcexa-casein glycomacropeptide. Y. Kawasaki et al., Inhibition by xcexa-Casein Glycomacropeptide and Lactoferrin of Influenza Virus Hemagglutination, Biosci. Biotech. Biochem. 57:1214-1215(1993).
U.S. Pat. No. 6,207,638 discloses a dry powder for enhancing satiety prior to a meal and extending satiety after a meal in a calorically efficient fashion. The dry powder was disclosed as containing 5.56-46.89% protein, 0.15-15.38% GMP, 5.56-46.8% oleic acid, 11.11-58.62% other long chain fatty acids, 5.56-46.89% soluble fiber and 2.70-37.36% insoluble fiber. The ""638 patent discloses that by stimulating CCK release and blocking the negative feedback mechanism of CCK release, satiety is enhanced with the consumption of fewer calories and satiation effects can be extended for up to three hours following a meal.
Thus, increased CCK levels have been found by ingestion of chitosan, as a result of binding bile acids, thereby inhibiting bile acid feedback that controls CCK release, and GMP, as result of stimulating CCK release and blocking the negative feedback mechanism of CCK release. However, until the present invention, no single composition could increase CCK levels using both chitosan and GMP. Therefore, there is a need to provide a single composition containing both chitosan and GMP, as well as related methods for appetite control.
The present invention is directed to a composition that satisfies the need for a single composition containing both chitosan and GMP, wherein the chitosan and GMP are in other than a cationic gum or polysaccharide/protein complex, as well as related methods for appetite control in a human and an animal.